Microphysiological systems (MPSs), or tissue chips, are a relatively new technology that have the potential to significantly impact the drug development process, as well as drug and chemical safety testing; however, adoption of these chips by industry and regulatory agencies has been slow due to a lack of confidence in the reliability and relevance of these models outside of their developer’s laboratories.

In the first National Institutes of Health (NIH)-funded study on tissue chip testing, researchers in the Texas A&M College of Veterinary Medicine (CVM) have taken measures to close that gap by completing an exhaustive, independent testing of the chips’ robustness and reproducibility.

Led by Courtney Sakolish, a postdoctoral trainee in toxicology, under the guidance of Ivan Rusyn, professor in the CVM’s Department of Veterinary Integrative Biosciences and principal investigator of the project, the study details the results of an investigation of tissue chip technology transfer and the reproducibility of tissue chip-derived data.

The research, “Technology Transfer of the Microphysiological Systems: A Case Study of the Human Proximal Tubule Tissue Chip,” which was funded by the NIH’s National Center for Advancing Translational Sciences (NCATS), was published on Oct. 5 in the online journal Scientific Reports. The study evaluated the kidney MPS developed by Ed Kelly and Jonathan Himmelfarb, at the University of Washington (UW) School of Pharmacy and Kidney Research Institute.

“Tissue chips have a lot of future applications, especially in the pharmaceutical industry, but we don’t really hear about any drugs being tested using these tissue chips because there really is not a lot of confidence in the use of these technologies just yet,” Sakolish said. “Our project worked on building confidence in the use of these models by extensively evaluating them.”

The final report establishes the reliability of the new test methods, defines the domain of applicability for these technologies, describes how test results should be interpreted in terms of a positive/negative response, and develops performance standards for the evaluation of relevant adverse outcomes.

“This is the first publication out of the NCATS funding we received in 2016 that shows that, yes, you can do that technology transfer,” Rusyn said. “Now we have a blueprint for how this could be done in the future, what the success looks like, and how this is not about the complexity of the actual engineered systems but how other factors, such as the availability of cells to put on these models, is really the most critical pitfall that frequently creates challenges with reproducibility.

“In this particular model, even though we were not replicating the whole kidney, we replicated a very important part of the kidney. We had cells that self-organized in the tubule and there was flow of media and cells that oriented themselves in a way very similar to how they are oriented in a living organism,” Rusyn said. “Not only do they look how they should, but they also function much more physiologically closer to in vivo. That’s where the excitement of this technology is. We can do a lot of experiments (with this MPS) that we can’t do in people.”

The team also worked in partnership with Cliff Stephan, the team’s core investigator at the Institute for Biosciences and Technology, part of the Texas A&M Health Science Center.

“Testing and validating issue chips is a very important step in translating basic science and engineering into understanding human disease and developing new therapies”, said Himmelfarb, a clinician and researcher at UW’s Kidney Research Institute.

“We learned a lot from this project and are to working with other academic partners, pharmaceutical companies, and governmental agencies to facilitate the translation of these technologies to the real world,” Sakolish said. “A very important aspect of this work is the collaboration between us and the developers and with the NIH, which recognizes that it takes a lot of work to bring these technologies to fruition. We are really grateful to the developers at the University of Washington and the NIH for their support.”

The kidney MPS was developed under NCATS award UH3TR000504. The tissue chip activities at Texas A&M were funded under NCATS award U24TR001950. The article can be found in Scientific Reports 8, article number 14882.